title: [The calix[4]arene C-107 is highly effective supramolecular inhibitor of the Na+,K(+)-ATPase of plasma membranes].
abstract: The inhibition of the Na+,K(+)-ATPase activity of the myometrium cell plasma membranes with calixarene C-107 (5,17-diamino(2-pyridyl) methylphosphono-11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix[4]arene) was investigated. It has been shown that calixarene C-107 reduced the Na+,K(+)-ATPase activity more efficiently than ouabain did, while it did not practically influence the "basal" Mg(2+)-ATPase activity of the same membrane. The magnitude of the cofficient of inhibition I0.5 was 33 +/- 4 nM, Hill coefficient was 0.38 +/- 0.06. The model calixarene C-150--the calixarene "scaffold" (26,28-dihydroxy-25,27-dipropoxycalix[4]arene), and the model compound M-3 (4-hydroxyaniline(2-pyridine)methylphosphonic acid)--a fragment of the calixarene C-107, had practically no influence on the enzymatic activity of Na+,K(+)-ATPase and Mg(2+)-ATPase. We carried out the computer simulation of interaction of calixarenes C-107 and the mentioned model compound with ligand binding sites of the Na+,K(+)-ATPase of plasma membrane and structure foundation of their intermolecular interaction was found out. The participation of hydrogen, hydrophobic, electrostatic and pi-pi (stacking) interaction between calixarene and enzyme aminoacid residues, some of which are located near the active center of Na+,K(+)-ATPase, was discussed.
authors.forename: O V
authors.initials: OV
authors.lastname: Bevza
authors.forename: T O
authors.initials: TO
authors.lastname: Veklich
authors.forename: O A
authors.initials: OA
authors.lastname: Shkrabak
authors.forename: R V
authors.initials: RV
authors.lastname: Rodik
authors.forename: V I
authors.initials: VI
authors.lastname: Kal'chenko
authors.forename: S O
authors.initials: SO
authors.lastname: Kosterin
mesh_terms: D000818:Animals; D001665:Binding Sites; D047250:Calixarenes / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013552:Swine
chemical_list: C582503:5,17-diamino(2-pyridyl) methylphosphono-11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalix(4)arene; D004791:Enzyme Inhibitors; D008024:Ligands; D063065:Organophosphonates; D047250:Calixarenes; D000254:Sodium-Potassium-Exchanging ATPase